This project proposed to morphologically and biochemically define the mechanism of action of vitamin A and its derivatives (retinoids) in altering epidermal differentiation in normal skin, and in benign and malignant lesions of skin. Topical all-trans retinoic acid, but not systemic 13-cis-retinoic acid, increased gap junction density and decreased desmosome density in treated basal cell carcinomas. This indicates that topical and systemic retinoids may exert their antineoplastic activity by different cellular mechanisms. A specific cytosol retinol binding protein (CRBP) has been identified in mouse, normal human skin and skin and human skin from patients with Darier's disease, psoriasis and basal cell carcinomas. A specific cytosol retinoic acid binding protein (CRABP) has also been identified in newborn mouse and normal human adult skin and newborn foreskin. The qualitative and quantitative distribution between the epidermis and dermis of both CRBP and CRABP has been determined in adult human lower limbskin.